791609-83-1Relevant articles and documents
Development of Gleevec Analogues for Reducing Production of β-Amyloid Peptides through Shifting β-Cleavage of Amyloid Precursor Proteins
Sun, Weilin,Netzer, William J.,Sinha, Anjana,Gindinova, Katherina,Chang, Emily,Sinha, Subhash C.
supporting information, p. 3122 - 3134 (2019/04/01)
Imatinib mesylate, 1a, inhibits production of β-amyloid (Aβ) peptides both in cells and in animal models. It reduces both the β-secretase and γ-secretase cleavages of the amyloid precursor protein (APP) and mediates a synergistic effect, when combined with a β-secretase inhibitor, BACE IV. Toward developing more potent brain-permeable leads, we have synthesized and evaluated over 75 1a-analogues. Several compounds, including 2a-b and 3a-c, inhibited production of Aβ peptides with improved activity in cells. These compounds affected β-secretase cleavage of APP similarly to 1a. Compound 2a significantly reduced production of the Aβ42 peptide, when administered (100 mg/kg, twice daily by oral gavage) to 5 months old female mice for 5 days. A combination of compound 2a with BACE IV also reduced Aβ levels in cells, more than the additive effect of the two compounds. These results open a new avenue for developing treatments for Alzheimer's disease using 1a-analogues.
A novel structure of the kinase inhibitors
-
Paragraph 0124; 0127; 0128, (2018/06/07)
The invention provides compounds of a novel kinase inhibitor as shown in the formula (I) or pharmaceutically acceptable salts, solvates, esters, acids, metabolites, combination drugs or prodrugs thereof. The compounds independently combines with at least
Discovery of 4-((N-(2-(dimethylamino)ethyl)acrylamido)methyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide (CHMFL-PDGFR-159) as a highly selective type II PDGFRα kinase inhibitor for PDGFRα driving chronic eosinophilic leukemia
Wang, Qiang,Liu, Feiyang,Qi, Shuang,Qi, Ziping,Yan, Xiao-E.,Wang, Beilei,Wang, Aoli,Wang, Wei,Chen, Cheng,Liu, Xiaochuan,Jiang, Zongru,Hu, Zhenquan,Wang, Li,Wang, Wenchao,Ren, Tao,Zhang, Shanchun,Yun, Cai-Hong,Liu, Qingsong,Liu, Jing
, p. 366 - 384 (2018/03/21)
Through exploration of the non-highly conserved allosteric hydrophobic pocket generated by DFG-out shifting in the inactive conformation, we discovered a highly selective type II PDGFRα kinase inhibitor 15i (CHMFL-PDGFRα-159), which exhibited strong poten
Phenylaminopyrimidine derivatives and methods of use
-
, (2008/06/13)
The present invention relates to phenylaminopyrimidine derivatives, processes for their preparation, pharmaceutical compositions containing them as active ingredient, methods for the treatment of disease states such as cancers associated with tyrosine kinases, especially Bcr-Abl, to their use as medicaments and to their use in the manufacture of medicaments for use in the production of inhibition of tyrosine kinase reducing effects in warm-blooded animals such as humans.
